Biohaven Receives FDA Complete Response Letter After Apotex API Issues

By Emily Forster -

July 26, 2019

Biohaven Pharmaceutical, a clinical-stage biopharmaceutical company, has received a Complete Response Letter (CRL) from the US Food and Drug Administration (FDA) for its 505 (b) (2) new drug application (NDA) for Nurtec (riluzole) for treating amyotrophic lateral sclerosis (ALS). The 505(b)(2) regulatory pathway is a type of NDA submission that can be used to obtain the approval of a new drug that contains similar active ingredients to a previously approved drug and is used for changes in dosage form, strength, route of administration, formulation, dosing regimen, or new indication.

The issue in the CRL relates to an FDA concern regarding the use of an active pharmaceutical ingredient (API) manufactured by Apotex Pharmachem India used in the bioequivalence study in 2017. The API was manufactured by Apotex between 2014 and 2016 and used in the drug-product supplies for the bioequivalence study. Concerns with manufacturing by Apotex recently led to the withdrawal of 31 Apotex drug products from the US market in July 2019, according to Biohaven.

Biohaven notes that the API for commercial supply of Nurtec is currently sourced from another supplier, with whom no chemistry, manufacturing and controls (CMC) issues have been identified. Further, the FDA did not cite any other concerns in its CRL regarding Nurtec.

In the CRL, the FDA stated that it provided recommendations to Apotex regarding the information that would be needed to qualify previous API batches manufactured at Apotex during the time period in question. Apotex did not provide Biohaven with notice of the FDA communication, either during the course of its bioequivalence trial or during the submission of its 505(b) (2) application for Nurtec.

Biohaven was subsequently informed by the manufacturer that it had an exemption from the FDA to supply riluzole to the US market during the time period. Biohaven says it has been in contact with the FDA’s chemistry, manufacturing and controls (CMC) group and Apotex to resolve the matter and it has submitted additional information to the FDA regarding this issue.

Biohaven says it will be working with the FDA to develop a timely path forward. While timelines are developed to resolve this matter, Biohaven said it will re-deploy the associated funds for Nurtec’s commercialization to other commercial needs of the organization.

Source: Biohaven Pharmaceutical